1. Pemphigus

2. Primary forms of Pemphigus
Deep Pemphigus (above Basal Cell Layer of Epidermis)
Pemphigus Vulgaris (most common and most severe)
Pemphigus Vegetans (rare Pemphigus Vulgaris variant)
Drug-Triggered Pemphigus (unmasks Pemphigus Vulgaris)
Superficial Pemphigus (involves Stratum Granulosum)
Pemphigus Foliaceus
Pemphigus erythematosus (Senear-Usher Syndrome)
Pemphigus herpetiformis

3. Secondary forms of Pemphigus
Paraneoplastic Pemphigus
Drug-Induced Pemphigus (similar to Pemphigus Foliaceus

4. PEMPHIGUS VULGARIS Accounts 70% of all pemphigus Etiology:
      Age: Middle age, rarely affects children
      Sex: Both sexes
      Races:Affects in eastern countries
      Association of other autoimmune disorders
Rheumatoid arthritis, Myasthenia gravis, Lupus erythematosus, Pernicious anaemia
Drugs: Penicillamine & Captopril

5. Uncommon but severe
Potentially fatal autoimmune disorder
Affects skin and mucous membrane.
Two major subtypes:
Pemphigus vulgaris
Pemphigus foliaceus

6. · Predisposition to genetic factors:
1. First-degree relatives of patients susceptible to the development of autoimmune diseases
2. Association with HLA-DR4
Immunological
1. Pemphigus vulgaris antigen: Desmoglein 3
2. Antibody titer: Antibodies of both IgG1 and IgG4
3. Passive transfer: Transplacental transfer of maternal pemphigus vulgaris antibodies may cause transient blisters in neonates.
4. Plasminogen-plasmin system involved in acantholytic process:IgG autoantibodies binds with epidermal intercellular material and the adjacent keratinocytes are induced to produced proteolytic enzymes which causes loss of adhesion and intraepidermal split and this process is known as acantholytic process.

7. Cause
All types of pemphigus are autoimmune diseases in which pathogenic IgG antibodies bind to antigens within the epidermis. The main antigens are desmoglein 3 (in pemphigus vulgaris) and desmoglein 1 (in superficial pemphigus). Both are cell-adhesion molecules of the cadherin family , found in desmosomes. The antigen–antibody reaction interferes with adhesion, causing the keratinocytes to fall apart.

8. Presentation
Pemphigus vulgaris is characterized by flaccid blisters of the skin and mouth and, after the blisters rupture, by widespread painful erosions. Most patients develop the mouth lesions first. Shearing stresses on normal skin can cause new erosions to form (a positive Nikolsky sign). In the vegetans variant heaped up cauliflower-like weeping areas are present in the groin and body folds. The blisters in pemphigus foliaceus are so superficial, and rupture so easily, that the clinical picture is dominated more by weeping and crusting erosions than by blisters. In the rarer pemphigus erythematosus, the facial lesions are often pink, dry and scaly.

9. Associated features and complications
Secondary infection
Extensive lesions associated with water and electrolyte imbalance
Complication of steroids and immunosuppresive drugs.

10. Mucosal lesions 1. Oral: 50-70% of patients
Intact bullae rare in the mouth
More commonly: ill-defined, irregularly shaped erosions on buccal, gingiva or palatine
2. Other mucosal surfaces: Conjunctive, Pharynx,
esophagus, nose,larynx, urethra, vulva and cervix

11. Cutaneous lesions: Localized or generalized
Morphology of lesion: Flaccid vesicles on normal skin or an erythematous base---- painful erosion--- heal without scarring -----hyperpigmentation
Site: Scalp, face, axillae, groins and pressure points

12. Nikolsky sign: positive
Lesions in skin folds: Vegetating granulations
Nail:
Dystrophies, acute paronychia, subungual haematomas

13. Course
The course of all forms of pemphigus is prolonged, even with treatment, and the mortality rate of pemphigus vulgaris is still at least 15%. Superficial pemphigus is less severe. With modern treatments, most patients with pemphigus can live relatively normal lives, with occasional exacerbations.

14. Pemphigus vegetans: Neumann type & Hallopeau type
A rare variant of pemphigus vulgaris
Characterized by vegetating erosions, primarily in flexures & oral lesions always present
Neumann type: Vesicles & bullae rupture---hypertrophic granulating erosions-- vegetating masses --edges studded with small pustules--erosions at the edge of the lesions induce new vegetation

15. Hallopeau type: Pustules--vegetating plaques- edges studded with small pustules
Prognosis:
Neumann type: Similar to P. vulgaris but prolonged.
Hallopeau type: More benign and spontaneous remission

17. Histology: Tzank smear: Spongiosis of basal cells of epidermis
followed by suprabasal cleft &
acantholytic cells ,basal cells
attached to basement membrane
Tzank smear:
Acantholytic cells

18. Direct immunofluorescence:
IgG in intercellular space of both involved and uninvolved skin (diagnostic)
Indirect immunofluorescence:
Circulating intercellular antibodies detected in most patients

19. Differential Diagnosis
Apthous ulcer
Bechet’s syndrome
Epidermolysis bullosa
Diagnosis is made by immunofluorescence and histological appearance of bulla.

20. Treatment · Good oral hygiene
·     
Good oral hygiene
·        Potassium permanganate and topical antiseptics
·        Candidal infection: topical imidazoles
·        Potent topical or intralesional steroids
Prednisolone: prednisolone 1.5mg/kg/day
·        Azathioprine 2.5mg/kg/day
·        Cyclophosphamide 1-3 mg/kg/day
·        Oral or intramuscular gold
·        Dapsone
·        Plasmapheresis
Treatment  

21. Prognosis · Treatment with systemic steroids reduced mortality 5-15%
Morbidity and mortality
Extent of disease,
Maximum dose of prednisolone required for remission
Presence of other disease
Older patients

22. PEMPHIGUS FOLIACEUS

23. Blistering is high in the epidermis, either in the granular layer or just beneath the stratum corneum
 Etiology:
Accounts 10-20% of pemphigus
Antigen: Desmoglein 1, a 160-kDa.
Histopathology: Superficial bullae high in the granular layer or immediately below the stratum corneum
Dyskeratotic cells in the granular

24. Clinical features Less severe
Onset: Insidious scaly lesions involving the 'seborrhoeic' areas
Scales separate leaving well-demarcated, crusted erosions surrounded by erythema
Erosions are both painful and offensive

25. PEMPHIGUS ERYTHEMATOSUS
Features of Lupus erythematosus and pemphigus
Oral mucosa rarely involved

26. Immunological features:
·  Granular IgG and C3 at BMZ
·  Intercellular IgG and C3 in the epidermis
Circulating antinuclear antibodies
Prognosis: Benign but chronic
Treatment:
·      Topical or intralesional steroids
·       Prednisolone mg/day

27. PARANEOPLASTIC PEMPHIGUS
Pemphigus associates with lymphoproliferative disease, thymomas or sarcomas
Clinical features
Overlap with erythema multiforme and lichen planus pemphigoides , Severe mucosal erosions
Polymorphous cutaneous signs
Histopathology:
Necrosis of keratinocytes or vacuolar interface dermatitis, Suprabasal clefting

28. DRUG INDUCED PEMPHIGUS
Drugs may exacerbate or induce pemphigus
Drugs: Thiol- Penicillamine & captopril
Non-thiol- enalapril, penicillins, cephalosporins
P. foliaceus and P.erythematosus: common patterns
Circulating auto-antibodies with the same antigenic specificities as in other forms of pemphigus
Prognosis: Recover spontaneously